Malignant mesothelioma is a very aggressive tumor and has been linked to occupational and environmental exposure to carcinogenic mineral fibers such as asbestos.Mesothelioma causes about 3,000 deaths per year in the U.S.and over 100,000 deaths per year worldwide.In the US it is estimated that more than 20 million people have been exposed to asbestos and are at risk of developing MM during the next decades.With the lack of effective strategies to diagnose,prevent and treat mesothelioma, median survival is only about 12 months from diagnosis.Therefore, novel approaches that target the onset and progression of this devastating malignancy are urgently needed.Recent studies have demonstrated the importance of asbestos-induced inflammation in the development and growth of mesothelioma.We identified HMGB 1 as the key initiator of this process.We discovered that asbestos induces cell necrosis, causing the release of HMGB 1.HMGB 1 functions as the "master switch" that when turned on, kick starts a series of inflammatory responses that over time may lead to malignant transformation of mesothelial cells and mesothelioma development.Moreover,mesothelioma cells are "addicted" to HMGB 1 even after the cells get transformed, and that HMGB 1 contributes to mesothelioma growth and progression.Novel strategies that interfere with HMGB 1-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including individuals genetically predisposed, and/or inhibit tumor growth.The very recent discovery that germline BAP 1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma and melanocytic tumors provides researchers with a novel target for prevention and early detection.